We plan to study several aspects of the clinical effects of marihuana. Our studies of the metabolism of cannabinoids by man will now be directed toward detecting within a few hours of exposure transitory urinary metabolites which may be useful for forensic purposes; the most likely candidate is unchanged tetrahydrocannabinol (THC) itself. We shall continue to explore structure-activity relationships of marihuana metabolites in man, as identified metabolites become available for such clinical testing. Interactions between THC and changes in neurotransmitters, for example acetylcholine, will be studied with an idea of obtaining some idea of the mechanism of action. The problem of variable responses to marihuana between different users will be examined in terms of psychological influences, such as set, and metabolic influences, such as the levels of drug-metabolizing enzymes. Physiological or biochemical effects of THC which may be of clinical importance, such as water retention due to antidiuresis, will be examined. Further appraisals will be made of potential therapeutic uses of THC or synthetic homologs of this material.